The genesis of renal necrosis developing during choline deficiency is being investigated. The generally held idea that choline deficiency causes an excess of catecholamines which results in renal ischemia and necrosis, has no evidence so far to support it. However, a 75% decrease in acetylochline content of kidneys of choline-deficient rats compared to controls has been reported by others. Other workers have reported that choline deficiency affects the renal lysosomes which begin to disintegrate. Degradative enzymes released could cause cellular damage and necrosis. Results to date are: 1) There does not appear to be any marked changes in catecholamine or electrolyte levels. However, there is an inverse relationship between excretion levels. For example, if urinary catecholamines are elevated, sodium excretion is down. Retention of sodium could be explained by decreased GFR or increased reabsorption of sodium. 2) Lysosomes from choline-deficient rats appear to be more permeable; i.e., more lysosomal enzymes (acid phophatase, aryl sulfatase, Beta-glucuronidase) are released from incubated choline- deficient rat renal lysosomes compared to controls, and more lysosomal enzymes appear in the urine of choline-deifcient rats. Ethyl alcohol potentiates the renal necrosis caused by choline deficiency. Experiments proposed for the coming year are to 1) continue experiments to verify the lysosomal enzyme work, 2) test an acetyl- seco-hemicholinium which block choline transport and could produce a choline-deficiency state faster, and 3) check renal function with renal clearances in choline-deficient and alcoholic rats.